Efficacy and Safety Clinical Study of RPH-104 in Adult Onset Still's Disease (AOSD)

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to evaluate the efficacy of RPH-104 when administered at a dose of 160 mg on Day 0, Day 7, Day 21 and then once every 2 weeks (Q2W) subcutaneous (SC) in patients with Adult Onset Still's Disease (AOSD). Furthermore, the study is scheduled to investigate pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RPH-104.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm International, LLC
• Collaborators: Data Management 365 LLC; Federal State Budgetary Educational Institution for Higher Education FSPbSMU n. a. I.P. Pavlov of the Ministry of Health of the Russian Federation; Pharmaceutical Analytics Center LLC; Scientific Center EFiS LLC

Criteria

Inclusion Criteria:

1. Presence of voluntarily signed and dated Informed Consent Form to participate in this study.

2. Definite diagnosis of Still's disease made on the basis of Yamaguchi diagnostic criteria (Yamaguchi M., 1992).

3. A patient with AOSD (with inactive disease / low disease activity / exacerbation).

4. In case of current GCs administration, their doses should be stable for at least 2 weeks prior to Day 0. Maximum acceptable dose calculated as 1 mg/kg/day is up to 60 mg/day.

5. In case of on-going methotrexate (MTX) administration, the dose should be stable for at least 4 weeks prior to Day 0. Maximum acceptable dose is 30 mg/week. In case of withdrawal of previous MTX administration, it should be made at least 4 weeks before Day 0.

6. Ability and willingness of the subject, according to the reasonable investigator's judgment, to attend the study site at all scheduled visits, undergo the study procedures and follow the protocol requirements including subcutaneous injections by qualified site personnel.

7. Consent of female subjects with childbearing potential, defined as all females with physiological potential to conceive (except for those with absolute termination of menses to be determined retrospectively after 12 months of natural amenorrhea, i. e. amenorrhea with relevant clinical status, e. g. appropriate age) to use highly effective contraception throughout the study starting from the screening (signed Informed Consent Form) and for at least 8 weeks after discontinuation of the study product administration; and negative pregnancy test (serum test for chorionic gonadotropin).

OR Consent of male subjects leading active sexual life to use highly efficient contraceptive measures throughout the study starting from the moment of signing the Informed Consent Form and for at least 8 weeks after the study product discontinuation.

Highly effective contraceptive method is defined as follows:

• complete abstinence: if complies with patients' preferable and habitual way of life. Periodic abstinence (e. g. calendar, ovulation, symptothermal, post-ovulation methods) and interrupted intercourse are not acceptable contraception methods;

• surgical intervention for female sterilization: bilateral ovariectomy (with/without hysterectomy) or tubal ligation at least 6 weeks prior to the study therapy initiation. In case of ovariectomy only, the female reproductive status should be verified by further hormonal test;

• surgical intervention for male sterilization (with a relevant documented lack of the sperm in the post-vasectomy ejaculate) at least 6 months prior to screening. For female subjects, a vasectomized sexual partner should be the only partner;

• combination of any two of the following methods (a+b or a+c or b+c):

1. oral, injection or implanted hormonal contraceptives; in case of oral contraceptives, the female subjects should administer the same product for at least 3 months prior to the study therapy;

2. intrauterine device or contraceptive system;

3. barrier contraception methods: a condom or occlusive cap (diaphragm or cervical cap/ vaginal fornix cap) with a spermicidal foam/ gel/ film/ cream/ vaginal suppository.

Exclusion Criteria:

1. Hypersensitivity to the investigational product (RPH-104) and/or its ingredients/excipients.

2. Previous administration of:

• rilonacept - less than 6 weeks prior to Day 0 of the study;

• canakinumab - less than 12 weeks prior to Day 0 of the study;

• anakinra - less than 1 week prior to Day 0 of the study;

• tumor necrosis factor alpha (TNF-a) antagonists, Interleukin 6 (IL-6) inhibitors
• less than 12 weeks prior to Day 0 of the study;

• Janus kinase inhibitors - less than 1 week prior to Day 0 of the study;

• immunosuppressants (azathioprine, cyclosporin, mycophenolate mofetil, tacrolimus, sirolimus, mercaptopurine, etc., except for methotrexate) - less than 24 weeks prior to Study Day 0;

• pulse therapy with GC (e. g., methylprednisolone 250-1000 mg/day intravenously or dexamethasone equivalent for 3 days) - less than 4 weeks (from the end of pulse therapy) to Study Day 0;

• any other biological product - less than 5 half-lives prior to Study Day 0.

3. Administration of live (attenuated) vaccine less than 3 months prior to Visit 1 (study treatment period initiation) and/or necessity to use such vaccine within 3 months after the study therapy discontinuation. Live attenuated vaccines include viral vaccines against: measles, rubella, parotitis, varicella, rotavirus, influenza (as nasal spray), yellow fever, poliomyelitis (oral polio-vaccine), tuberculosis vaccine (BCG), typhoid (oral typhoid fever vaccine) and camp fever (epidemic typhoid vaccine). Immunocompetent family members should refuse to use oral polio-vaccine throughout the subject's participation in the study.

4. Conditions or signs which, according to the investigator, suggest impaired (reduced) immune response and/or significantly increase the risk of immunomodulating therapy including (but not limited to):

• 4.1. active bacterial, fungal, viral or protozoal infection at screening onset;

• 4.2. opportunistic infections and/or Kaposi's sarcoma at the screening period onset;

• 4.3. chronic bacterial, fungal or viral infection requiring systemic therapy with parenteral products at the main screening period onset;

• 4.4. human immunodeficiency viruses (HIV), hepatitis B or C.

5. Active infection of M. Tuberculosis, as per examination results: positive QuantiFERON-TB/SPOT.TB test at screening, chest X-ray findings confirming pulmonary tuberculosis during screening.

• At discretion of certified tuberculosis specialist or pulmonologist specialized in diagnosing and treatment of tuberculosis, a patient with latent tuberculosis can be included in the study during the preventative treatment of latent tuberculosis infection in compliance with local recommendations.

6. Any other relevant concomitant diseases (cardiovascular, nervous, endocrine, urinary, gastrointestinal, hepatic disorders, hemostatic disorders, other autoimmune diseases, etc.) or conditions which, according to the investigator's judgment, may affect the subject's participation or well-being in the study and/or distort assessment of the study results.

7. History of organ transplantation or necessity in transplantation at the screening onset.

8. Any malignancies during the screening period or for 5 years before screening except for non-metastatic basal cell and squamous cell skin cancer after total resection or in situ carcinoma of any type after total resection.

9. Psychiatric disorders which, according to the justified investigator's judgment, may affect the subject participation in the study and his/her ability to follow the protocol procedures.

10. Pregnancy or breast-feeding.

11. History of alcohol or psychoactive substances abuse, according to the investigator's evaluation.

12. Severe renal failure: Cockroft-Gault creatinine clearance (ClCr) < 30 mL/min.

13. Any of the deviations in the laboratory tests below:

• absolute neutrophil count < 1.5 х 10^9/L;

• white blood cells (WBC) count < 3.5 х 10^9/L;

• platelet count < 100 х 10^9/L;

• hemoglobin level ≤ 80 g/L;

• glycated hemoglobin (HbA1c) ≥ 8 %);

• alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 8.0 x upper limits of normal (ULN);

• AST and/or AST > 3 x ULN with increased bilirubin > 1.5 x ULN;

• bilirubin > 1.5 x ULN (except for confirmed Gilbert's disease).

14. Uncontrolled diabetes mellitus.

15. Concomitant participation in other clinical studies at the screening onset or administration of any unauthorized (investigational) products less than 4 weeks or 5 half-life periods (whichever is longer) before Visit 1 (treatment initiation in the study).

16. Macrophage activation syndrome (MAS) in the history or suspected at screening.

17. MAS diagnosed within the last 2 months prior to Day 0.

18. Previous participation in this clinical study if at least one dose of the investigational product has been received.